P3399Influence of TCF21 rs12190287 in the coronary artery disease risk prediction. An association study in a Portuguese population

• Published in: European heart journal 2019-10, Vol.40 (Supplement_1)
• Main Authors: Sousa, J, Mendonca, M, Pereira, A, Mendonca, F, Monteiro, J, Neto, M, Sousa, A C, Henriques, E, Freitas, S, Guerra, G, Borges, S, Ornelas, I, Drumond, A, Palma Dos Reis, R
• Format: Article
• Language: English
• ISSN: 0195-668X; 1522-9645
• DOI: 10.1093/eurheartj/ehz745.0275

Abstract TCF21 is a member of the basic-helix-loop-helix (bHLH) transcriptor factor family, being critical for embryogenesis of the heart, kidney and spleen. TCF21 also regulates epicardium-derived cells differentiation into smooth muscle and fibroblast lineages. Aim Investigate the impact of TCF21 rs12190287 in the prediction and discrimination of CAD risk, individually or into a genetic risk score (GRS) formed by a set of 13 genetic variants. Methods We performed a case-control study with 3050 subjects (1619 coronary patients with 53.3±8 years; 78.9% male and 1431 controls with 52.8±8 years; 76.6% male) from GENEMACOR study. We investigated all traditional risk factors (TRF), as well as 13 genetic variants from GWAS with unknown pathophysiological pathway so far, including TCF21 (rs12190287), ZC3HC1 (rs11556924), PSRC1/SORTI (rs599839), PHACTR1 (rs1332844), MIA3 (rs17465637), SMAD3 (rs17228212), ZNF259 (rs964184), ADAMTS7 (rs3825807), CDKN2B (rs4977574), 9p21.3 (rs1333049), KIF6 (rs20455), PCSK9 (rs2114580) and GJA4 (rs618675). A multiplicative genetic risk score with these 13 genetic variants (m13GRS), was calculated. Subsequently, two logistic regressions were performed; primarily with all the TRF and all the genes individually and the second with TRF and m13GRS. Results The first multivariate analysis shows that, besides the strong association of the TRF with CAD risk (with smoking status on the top of the list, with an OR of 3.2; p